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Objective:To observe the prevention and control effect of 1% atropine on the progression of form deprivation myopia (FDM) in guinea pigs and the potential biological mechanism.Methods:Sixty-nine 3-week-old tricolor guinea pigs with normal refraction were randomly divided into a normal control group ( n=19), a FDM group ( n=19), a FDM+ atropine group ( n=19), and an atropine group ( n=12). No intervention was given to guinea pigs in normal control group.The FDM model was established by covering the right eye of guinea pigs with a semitransparent latex facemask for 4 weeks in FDM and FDM+ atropine groups.For the FDM+ atropine group, 1% atropine gel was topically administered to the form-deprived right eyes once a day for 4 weeks.For the atropine group, the right eye was treated with 1% atropine gel once a day for 4 weeks.Refraction and axial length of guinea pigs were measured by retinoscopy and ophthalmic A-scan ultrasonography respectively at baseline, experiment week 2 and week 4.In experiment week 4, eyeballs were enucleated to make sections via the paraffin wax processing procedure, and the microstructural and ultrastructural changes of the sclera were observed under the light microscope and transmission electron microscope, respectively.The isobaric tags for relative and absolute quantitation labeling combined with liquid chromatography-tandem mass spectrometry were used to identify the differentially expressed proteins.Use and care of the animals complied with the Regulation for the Administration of Affairs Concerning Experiment Animals by State Science and Technology Commission.The study protocol was approved by the Institutional Animal Care and Use Committee of Tianjin Medical University (No.TJYY2020111028). Results:There were statistically significant differences in the diopter of guinea pigs at different time points among the four groups ( Fgroup=138.892, P<0.001; Ftime=167.270, P<0.001). Compared with normal control group, the diopter of guinea pigs in FDM group at experiment weeks 2 and 4, and FDM+ atropine group at experiment week 4 developed toward myopia, showing statistically significant differences (all at P<0.001). Compared with FDM group, the diopter of guinea pigs in FDM+ atropine group at experiment weeks 2 and 4 developed toward hyperopia, showing statistically significant differences (both at P<0.001). There were statistically significant differences in the axial length of guinea pigs at different time points among the four groups ( Fgroup=32.346, P<0.001; Ftime=353.797, P<0.001). The axial lengths of FDM group at experiment weeks 2 and 4 and FDM+ atropine group at experiment week 4 were longer than those of normal control group, and the axial lengths in FDM+ atropine group at experiment weeks 2 and 4 were shorter than those in FDM group, and the differences were statistically significant (all at P<0.001). The collagenous fibers of posterior sclera of guinea pigs were loose and disordered in FDM group, and were regular in FDM+ atropine group.The posterior scleral thickness of normal control group, FDM group, FDM+ atropine group and atropine group was (141.74±16.98), (101.46±9.15), (112.74±6.24) and (134.30±18.19) μm, respectively, with a statistically significant difference ( F=6.709, P=0.005). The posterior sclera was significantly thinner in FDM group than in normal control group and FDM+ atropine group (both at P<0.05). The diameter of posterior scleral collagen fiber gradually increased from inside to outside in normal control group, FDM+ atropine group and atropine group, and the diameters of the inner, middle and outer posterior scleral collagen fibers were smaller in FDM group than in normal control group.Proteomic analysis revealed 85 differentially expressed proteins (fold change>1.30) between FDM group and normal control group, FDM+ atropine group and FDM group, of which 38 were up-regulated and 47 were down-regulated after atropine treatment.Gene Ontology enrichment analysis showed that biological processes mainly involved were biological regulation, cell process, localization and metabolic process.Molecular function mainly involved were binding, catalytic activity, molecular function regulator, structural molecule activity and transporter activity.Cell components mainly involved were in cellular anatomical entity, intracellular and protein-containing complex. Conclusions:Atropine can increase the diameter of scleral collagen fibers in guinea pigs of FDM model, improve the arrangement of scleral collagen fiber, inhibit scleral thinning.The mechanism of atropine to control myopia progression is closely related to the tight junction between scleral cells, cytoskeleton and extracellular matrix remodeling.
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Objective To study the binding performance of 99Tcm labeled anti-human prostatic specific membrane antigen (PSMA) monoclonal antibody J591 (99Tcm-J591) and prostate cancer cells in vitro,the biodistribution and SPECT imaging of 99Tcm-J591 in nude mice bearing human prostate cancer in vivo.Methods The monoclonal antibody J591 was labeled with 99Tcm by improved Schwarz method.Labeled antibody was purified by Sephadex G-50.The labeling efficiency and radiochemical purity were measured by paper chromatography and trichloroacetic acid method.The binding performance of J591 and prostate cancer cells was measured by flow cytometry in vitro.The nude mice bearing PSMA-positive C4-2 prostate carcinoma xenografts served as experiment group,mice bearing PSMA-negative PC3 tumors served as control group.6.2-8.5 MBq of 99Tcm-J591 (25 μg) was intravenously injected into mice.Gamma imaging was performed 2,6,12 and 24 h after injection,T/NT was calculated by ROI technique.After scanned 12 h post injection,4 mice of the experiment group and 5 mice of the control group were sacrificed and the tracer in vivo biodistribution was measured by gamma-counting,and the ％ ID/g was calculated.Two-sample t test was carried out to validate significant difference of ％ID/g between two groups.Results The labeling efficiency and radiochemieal purity of 99Tcm-J591 were (78.9±6.2)％ and (92.3±5.1)％,respectively,and the specific activity of 99Tcm-J591 was 68.7 MBq/mg.The antibody J591 and 99Tcm-J591 could strongly combine with PSMA-positive C4-2 cells in vitro,and didn't combine with PSMA-negative PC3 cells in vitro.SPECT imaging results showed that radioactive concentration was obvious in tumor 6 h post injection,the concentration scope became large and the tumor image was clear 12 h post injection.T/NT was 1.9±1.1 at 2 h,4.3±1.8 at 6 h,5.6±2.7 at 12 h,1.4±0.6 at 24 h,respectively.In the control group,no radioactivity concentration was found in tumor,and T/NT was less than 2.The biodistribution results showed that ％ID/g of tumor tissue was 20.1±5.2 in the experiment group and 5.8±2.6 in the control group,and there was significant difference (t=5.37,P＜0.001).No significant tracer uptake occurred in other tissues and organs between the two groups (all t＜ 1.98,all P＞0.05).Conclusion The immunoactivity,characteristics of biodistribution and tumor targeting property of monoclonal antibody J591 show promising future and potential values in diagnosis and therapy of prostate cancer.
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To investigate the risk of papillary thyroid carcinoma (PTC) in patients with nontoxic multinodular goiter (MNG) compared to that in patients with solitary nodule (SN).From Jan 2006 to Dec 2011,761 patients underwent thyroid surgery were included in the retrospective study.According to pathology,patients were subdivided into two groups,MNG and SN.Preoperative thyroid profiles were correlated with patients' postoperative diagnoses.In whole group,the risk of PTC was significantly lower in MNG than in SN (7.09％ vs 15.58％,P =0.000 9).In patients with nontoxic multinodular goiter,the risk of PTC was lower compared to that of those with SN.